Effects of Hydroxyurea on Fertility in Sickle Cell Disease; A Systemic Review and Meta-Analysis
Notice bibliographique
Résumé
Background: Hydroxyurea (HU) remains a widely available and clinically effective therapy for sickle cell disease (SCD). Whilst a substantial body of evidence documents the benefits of HU with acceptable short- and long-term toxicity profiles, concerns regarding its safety persist, particularly regarding fertility. Methods: This systemic review and meta-analysis evaluated fertility parameters in males and females with SCD receiving HU therapy. Articles published from inception to July 2023 were searched in PubMed and EMBASE. Terms used in the research for primary endpoints were “”sickle cell disease“ and ”infertility“ and ”hydroxyurea“; ”sickle cell disease“ and ”fertility“ and ”hydroxyurea“; ”sickle cell anaemia“ and ”hydroxyurea“ and ”infertility“; ”sickle cell disease“ and ”hydroxycarbamide“ and ”infertility“; and combination of the terms ”sickle cell anaemia“ and ”hydroxycarbamide“ and ”infertility“. Our research focused on primary fertility outcomes stratified by male or female gender. Inclusion criteria were as follows: (i) Studies published in English from inception to the present day; (ii) Studies subjects (aged ≥ 6 years), prospective and retrospective cohort studies reporting frequency of outcomes of interests (semen parameters and female infertility events) stratified by HU therapy. Case reports, reviews, animal studies, duplications and studies on very young patients (aged < 6 years) were excluded . The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of the included studies. Results: A total of 160 articles were initially retrieved from PubMed and Embase. After applying the exclusion criteria, the full texts of 32 potentially relevant studies were reviewed. A total of 25 were excluded due to lack of relevant research (n=11), non-human research (n=4), not original research (n=6), case reports (n=3) and articles not in English (n=1). In total, 7 were finally included for meta-analysis (Figure). Four studies were included that evaluated the effects of HU on sperm parameters in males. Three studies were included that assessed anti-mullerian hormone (AMH) levels and ovarian reserves in females. Changes from baseline were used to identify compromised fertility. Amongst males, HU treatment negatively impacted the concentration of spermatozoa (MD= -15.48 million/mL; 95% CI: [-20.69, -10.26]; p< 0.001) which continued following treatment cessation (MD= -20.09 million/mL; 95% CI: [-38.78, -1.40]; P= 0.04). HU treatment also led to lower total sperm counts (MD= -105.87 million; 95% CI: [-140.61, -71.13]; P< 0.001) which persisted after treatment cessation (MD= -53.05 million; 95% CI: [-104.96, -1.14]; P= 0.05). Sperm volume, initial forward motility and morphology were unaffected by HU treatment. In females, HU treatment did not impact the mean AMH levels 2.01 (95% CI [1.58, 2.44] and a total of 67% patients treated with HU showed normal ovarian reserves (95% CI [53%, 82%]). The fertility of 33% of patients was however negatively impacted by HU therapy. Conclusions: Our findings suggest that the use of HU for SCD impacts seminal fluid parameters in males and diminishes ovarian reserves in a significant number of females. Fertility preservation counselling should be considered in patients with SCD in both genders of reproductive age prior to HU therapy. Our study highlights the need for long-term multi-centric studies using consistent HU doses and outcome assessments to fully understand the impact of HU on fertility in SCD patients.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,009 | 0,021 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,015 | 0,031 |
| Bibliométrie | 0,007 | 0,008 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,003 | 0,001 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».